Even with high speed rail, I think East Coast - Chicago is pushing it on being time competitive. I suspect that the most likely HSR would have an end to end average of 80 - 100 mph (the Acela end-to-end average between New York and DC is about 80 mph), which means that the trip would be shortened from the current 18 - 20 hours to maybe 8 - 10 hours. Even with driving to the airport, TSA lines, waiting at the baggage carousel, etc., the 2 hour flights between the east coast and Chicago are still way faster.
And, of course, high speed rail would need brand new infrastructure that costs billions, especially the Philadelphia - Pittsburgh and Washington to Pittsburgh routes that have to cross the Appalachian Mountains. All kinds of crazy expensive viaducts, cuttings and tunnels would be needed to straighten out the route to allow for high speed running. On top of the fancy trackwork and specialized signaling needed for high speed operations. The New York to Chicago Water Level Route via Albany and Buffalo doesn't have the topograhical problems, but it is longer, so the point to point times won't be as fast, and the trains wouldn't serve Philadelphia, Baltimore and Washington (plus everything in between), the the market would be more limited.
If you were going to bite the financial bullet and do real high speed rail, the optimal way would be to base the route on the old Broadway limited, running it through Philly and Harrisburg and routing the new high speed rail track through State College, bypassing Huntingdon.
Probably the best option to improving service on this corridor is incremental improvements (like extra tracks and improved signaling) to allow a 60 mph end-to-end average speed (as opposed to the current 45 - 50 mph) on all three corridors (Water Level Route, old PRR Maine Line, and the B&O route from Washington), and extra service timed at the opposite ends of the days from the current service. This would allow daylight service between Ohio and the East Coast (which might be competitive with flying -- at our work, we started driving to visit our contractors in the Akron area rather than flying, it was much more convenient, as well as cheaper), as well as daylight service between Ohio and Chicago. Also, frequent corridor service between Pittsburgh -- Cleveland -- Toledo, and maybe Cleveland-Buffalo, too, though I've never driven that interstate and don't know how heavy the traffic is.